Efficacy of sucroferric oxyhydroxide treatment in Japanese hemodialysis patients and its effect on gastrointestinal symptoms.

Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphatemia in adult dialysis patients. Studies in Japan about the side effects of SFOH treatment indicate that the incidence of diarrhea (25%) is greater while that of constipation (2.9%) is lesser in comparison to that observed upon treatment with an existing phosphate binder. In the present study, the effect of treatment with a combination of the existing phosphate binders and SFOH on the serum phosphorus level and digestive symptoms was observed in hemodialysis patients with hyperphosphatemia, which is untreatable using only the existing phosphate binders. We evaluated the serum phosphorus levels and gastrointestinal symptoms (using the gastrointestinal symptom rating scale) of 6 patients (2 men, 4 women) before and 2, 4, 6, and 8 weeks after continuous administration. The serum phosphorus levels before and 2, 4, 6, and 8 weeks after combination treatment were 7.4±1.0 mg/dL, 5.9±1.3 mg/dL, 5.8±1.5 mg/dL, 5.8±1.4 mg/dL, and 5.8±1.3 mg/dL, respectively, with significant reduction in the levels being observed 2 weeks after administration (p<0.05) and persisting even 8 weeks after continuous administration. The constipation scores before and 2, 4, and 8 weeks after drug administration were 2.39±0.85, 2.34±1.93, 2.56±1.44, and 3.28±2.19, respectively, with no changes observed during the investigation period. The diarrhea scores before and 2, 4, and 8 weeks after drug administration were 2.22±0.91, 2.06±1.16, 1.28±0.39, and 1.06±0.13 respectively. The scores improved significantly, 4 weeks after drug administration (p<0.05), and the improvement persisted, even 8 weeks after continuous administration. Thus, by using a combination of the existing phosphate binders and SFOH, we were able to reduce the serum phosphorus level in patients with hyperphosphatemia, which is untreatable using the existing phosphate binder alone, with no sign of exacerbation of the gastrointestinal symptoms despite a few contradictory case reports.

Gastrointestinal symptoms after the substitution of sevelamer hydrochloride with lanthanum carbonate in Japanese patients undergoing hemodialysis.

Lanthanum carbonate has the same phosphorus depressant effect as the other phosphorus adsorbents, and is expected to decrease digestive symptom onset such as constipation in Japanese patients undergoing hemodialysis compared to sevelamar hydrochloride. In this study, we investigated the short- and long-term changes in digestive symptoms in these patients after substituting sevelamar hydrochloride with lanthanum carbonate. We studied 16 patients (4 men, 12 women) and evaluated their gastrointestinal symptoms before administration, at the time of administration, and 2, 4, 8, and 12 weeks after administration, using the Gastrointestinal Symptom Rating Scale. In addition, we conducted repeat evaluations 52 weeks after administration for the patients in whom lanthanum carbonate was administered continuously for 52 weeks. Fourteen (87.5%) out of the 16 patients could tolerate continuous administration for 12 weeks. The constipation score was 3.21 ± 1.74 before administration, 2.07 ± 0.83 2 weeks after administration, 1.76 ± 0.83 4 weeks after administration, 1.57 ± 0.56 8 weeks after administration, and 11.41 ± 0.48 12 weeks after administration. The scores improved significantly 4 weeks after administration (p < 0.05) and even 12 weeks after continuous administration. Among the 16 study patients, 9 patients (1 men, 8 women) were received lanthanum carbonate continuously for 52 weeks. The constipation score was 3.74 ± 1.92 at the start of administration, 1.37 ± 0.56 12 weeks after administration, and 1.85 ± 0.63 52 weeks after administration, with significant improvement even 52 weeks after administration (p < 0.05). This study shows that substituting sevelamar hydrochloride with lanthanum carbonate improves constipation symptoms in hemodialysis patients from an early stage, which indicates its usefulness in improving constipation symptoms caused by sevelamar hydrochloride.

Influence of cerebral fluid drainage on the pharmacokinetics of vancomycin in neurosurgical patients.

The objective of this study was to retrospectively investigate the influence of cerebral fluid drainage on the serum concentrations and pharmacokinetic parameters of vancomycin (VCM). We analyzed 55 patients with normal renal function who had been hospitalized in the neurosurgical ward and received intravenous infusions of VCM. We compared the daily doses of VCM, serum VCM concentrations, serum concentration/dose ratio (C/D ratio), and pharmacokinetic parameters calculated using the Sawchuk-Zaske method between patients who underwent cerebral fluid drainage (drainage group) and controls (non-drainage group). The patients in the drainage group showed a significantly lower trough concentration of VCM (5.8 ± 3.3 µg/mL) than that shown by the non-drainage group (9.9 ± 5.4 µg/mL, p = 0.017). Further, the patients in the drainage group showed a significantly lower trough C/D ratio (0.32 ± 0.17) than that shown by the non-drainage group (0.50 ± 0.31, p = 0.047). In conclusion, cerebral fluid drainage may influence VCM pharmacokinetics. Our findings strongly suggest that a high dose of VCM is required to maintain optimal serum concentrations of VCM in patients managed with cerebral fluid drainage.

The association between risk factors and time of onset for thrombocytopenia in Japanese patients receiving linezolid therapy: a retrospective analysis.

WHAT IS KNOWN AND OBJECTIVE: Linezolid (LZD) is an oxazolidinone antibiotic that is active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The major adverse effect related to its use in humans is reversible myelosuppression, which mostly manifests as thrombocytopenia. This retrospective study was conducted to identify risk factors that might contribute towards the development of thrombocytopenia due to intravenous administration of LZD. METHOD: Patients who were administered LZD between January 2008 and March 2013 were included. Thrombocytopenia was defined as a decrease in platelet count of ≥10 × 10(4) cell/µL from baseline or of ≥30%. RESULTS: A total of 47 patients were included in this study. These patients were divided into two groups: 22 patients (46·8%) were assigned to a non-thrombocytopenia group and 25 patients (53·2%) to a thrombocytopenia group. Multivariate logistic regression analysis revealed significant intergroup differences in duration of LZD treatment [odds ratio (OR) = 1·278; 95% confidence interval (CI) = 1·068-1·529; P = 0·007] and white blood cell (WBC) count (>12000 cells/µL; OR = 10·399; 95% CI = 1·667-64·882; P = 0·012). WHAT IS NEW AND CONCLUSIONS: This finding suggests that duration of LZD treatment and WBC count (>12000 cells/µL) are risk factors associated with thrombocytopenia resulting from LZD administration.